Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: Implications for treating stress urinary incontinence
Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: Implications for treating stress urinary incontinence
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DOI：
10.1016/s0090-4295(03)00754-4
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发表时间：
2003-10-01
期刊：
影响因子：
2.1
通讯作者：
Thor, KB
中科院分区：
文献类型：
--
作者：
Thor, KB
压力性尿失禁（SUI）是最常见的尿失禁形式，仍然是一个在很大程度上诊断不足的问题，给许多妇女带来了巨大的经济和生活质量负担，但几乎没有治疗选择。正在进行的动物和早期人类研究表明，单胺神经递质在控制尿道储存和排尿反射中起关键作用。在骶脊髓的Onuf核中发现的运动神经元控制尿道功能，并且具有将它们与其他运动神经元区分开的几个独特性质。首先，神经元均匀地小于周围的其他运动神经元，并且具有成束的树突，从而允许强烈的同步激活或抑制。其次，神经元表现出独特的神经化学特征。与周围区域的神经元不同，Onuf核的运动神经元具有密集的去甲肾上腺素能和肾上腺素能终末。动物研究表明，Onuf核中的α（1）-肾上腺素受体和5-羟色胺（5-HT）受体促进括约肌收缩。刺激这些受体的激动剂促进保护或失禁反射，而阻断受体的拮抗剂抑制该反射。因此，加强5-HT和去甲肾上腺素（NE）的作用，以增强括约肌活动可能是临床上有希望改善SUI的症状。重要的是，括约肌神经元的活性可以在尿液储存期间增加，而不会干扰膀胱括约肌协同作用。给予5-HT/NE摄取抑制剂度洛沙汀在膀胱充盈期间促进括约肌收缩，但在排尿时膀胱收缩期间不促进。度洛沙汀的这种独特作用可能通过5-HT和NE对神经递质谷氨酸激活括约肌运动神经元的选择性神经调节作用来维持。用度洛沙汀延长NE和5-HT的自然释放作用，可增强机体控制储尿和排尿的正常过程。早期试验表明，度洛沙汀可显著减少尿失禁发作，并且在临床环境中耐受性良好。(C)2003年爱思唯尔公司
Stress urinary incontinence (SUI), the most common form of incontinence, continues to be a largely underdiagnosed problem that imposes large financial and quality-of-life burdens on many women but has few treatment options. Ongoing animal and early human studies have shown that monoamine neurotransmitters play key roles in controlling urethral storage and micturition reflexes. Motor neurons found in the Onuf nucleus of the sacral spinal cord control urethral function, and have several unique properties that distinguish them from other motor neurons. First, the neurons are uniformly smaller than other surrounding motor neurons and have bundled dendrites, allowing strong synchronous activation or inhibition. Second, the neurons demonstrate unique neurochemical profiles. Unlike neurons in surrounding areas, the motor neurons of the Onuf nucleus have dense populations of noradrenergic and serotonergic terminals. Animal studies have shown that alpha(1)-adrenoceptors and serotonin (5-hydroxytryptamine [5-HT]) receptors in the Onuf nucleus facilitate sphincter contraction. Agonists that stimulate these receptors facilitate the guarding or incontinence reflex, whereas antagonists that block the receptors inhibit this reflex. Therefore, boosting the effects of 5-HT and norepinephrine (NE) to enhance sphincter activity could be clinically promising for improving the symptoms of SUI. Importantly, the activity of the sphincter neurons can be increased pharmacologically during urine storage without interfering with bladder-sphincter synergy. Administering the 5-HT/NE uptake inhibitor duloxetine facilitates sphincter contraction during bladder filling but not during bladder contraction in micturition. This unique effect of duloxetine may be maintained by the selective neuromodulatory effects of 5-HT and NE on activation of sphincter motor neurons by the neurotransmitter glutamate. Prolonging the effect of naturally released NE and 5-HT with duloxetine could augment the body's normal processes for controlling urine storage and micturition. Early trials have demonstrated that duloxetine significantly reduces incontinence episodes and is well tolerated in the clinical setting. (C) 2003 Elsevier Inc.